This proposal focuses on our efforts to understand molecular mechanisms regulating memory formation. It has been previously shown that cAMP response element binding protein (CREB)-mediated transcription is required in long-term plasticity and this phenomenon is conserved from mollusks to mammals although the presence of multiple CREB forms in mammals complicates interpretation of results obtained from study of CREB mutant mice. The proposed research will involve study of transcription- dependent synaptic plasticity which underlies learning and memory processes. The generated mutant mice will allow for genetic control of CREB-dependent gene expression in hippocampal neurons, and study the molecular and cellular mechanisms of the transition from short- to long-term memory. Mutant mice will be challenged in several learning and memory paradigms which are known to be dependent on the integrity of hippocampus. A newly created mouse model will provide the unique approach to study memory consolidation at molecular, cellular and cognitive level.